Invasive infection usually results in meningococcemia, meningitis, or both. Onset often is abrupt in meningococcemia, with fever, chills, malaise, myalgia, limb pain, prostration, and a rash that initially can be macular, maculopapular, petechial, or purpuric. The maculopapular and petechial rash is indistinguishable from the rash caused by viral infections, and the purpuric rash may occur in severe sepsis as a result of other bacterial pathogens, including Streptococcus pneumoniae . The progression of disease often is rapid. In fulminant cases, purpura, limb ischemia, coagulopathy, pulmonary edema, shock (characterized by tachycardia, tachypnea, oliguria, and poor peripheral perfusion, with confusion and hypotension late in the disease), coma, and death can ensue in hours despite appropriate therapy. Signs and symptoms of meningococcal meningitis are indistinguishable from signs and symptoms of acute meningitis caused by S pneumoniae or other meningeal pathogens. In severe and fatal cases of meningococcal meningitis, raised intracranial pressure is a predominant presenting feature. The case-fatality rate for meningococcal disease is 10%, and death is associated with young age, absence of meningitis, coma, hypotension, leukopenia, and thrombocytopenia. Less common manifestations include pneumonia, febrile occult bacteremia, conjunctivitis, septic arthritis, and chronic meningococcemia. Invasive meningococcal infections can be complicated by arthritis, myocarditis, pericarditis, and endophthalmitis. A self-limiting postinfectious inflammatory syndrome occurs in less than 10% of cases 4 or more days after onset of meningococcal infection and most commonly presents as fever and arthritis or vasculitis. Iritis, scleritis, pericarditis, and polyserositis are less common manifestations.
Sequelae associated with meningococcal disease occur in 11% to 19% of patients and include hearing loss, neurologic disability, digit or limb amputations, and skin scarring.
Neisseria meningitidis is a gram-negative diplococcus with at least 13 serogroups based on capsule type.
Strains belonging to groups A, B, C, Y, and W-135 are implicated most commonly in invasive disease worldwide. Serogroup A has been associated frequently with epidemics outside the United States, primarily in sub-Saharan Africa. An increase in cases of serogroup W-135 meningococcal disease has been associated with the Hajj pilgrimage in Saudi Arabia. Since 2002, serogroup W-135 meningococcal disease has been reported in sub-Saharan African countries during epidemic seasons. An unprecedented increase in cases of serogroup X meningococcal disease was observed in Niger in 2006. Recent prolonged outbreaks of serogroup B meningococcal disease have occurred in New Zealand, France, and Oregon.
The distribution of meningococcal serogroups in the United States has shifted in the past 2 decades. Serogroups B, C, and Y each account for approximately 30% of reported cases, but serogroup distribution varies by age, location, and time. Approximately three quarters of cases among adolescents and young adults are caused by serogroups C, Y, or W-135 and potentially are preventable with available vaccines. In infants, more than 50% of cases are caused by serogroup B and are not preventable with vaccines available in the United States.
Since introduction in the United States of Haemophilus influenzae type b and pneumococcal polysaccharide-protein conjugate vaccines for infants, N meningitidis has become the leading cause of bacterial meningitis in children and remains an important cause of septicemia. Disease most often occurs in children 2 years of age or younger; the peak attack rate occurs in children younger than 1 year of age. Another peak occurs in adolescents 15 through 18 years of age. Freshman college students who live in dormitories and military recruits in boot camp have a higher rate of disease compared with people who are the same age and are not living in such accommodations. Close contacts of patients with meningococcal disease are at increased risk of becoming infected. Patients with deficiency of a terminal complement component (C5-C9), C3 or properdin deficiencies, hypogammaglobulinemia, or anatomic or functional asplenia are at increased risk of invasive and recurrent meningococcal disease. Patients are considered capable of transmitting the organism for up to 24 hours after initiation of effective antimicrobial Treatment. Asymptomatic colonization of the upper respiratory tract provides the source from which the organism is spread. Transmission occurs from person to person through droplets from the respiratory tract and requires close contact.
Outbreaks have occurred in communities and institutions, including child care centers, schools, colleges, and military recruit camps. An increased number of meningococcal outbreaks in the United States were reported during the 1990s. However, most cases of meningococcal disease are endemic, with fewer than 5% associated with outbreaks. Outbreaks often are heralded by a shift in the distribution of cases to an older age group. Serologic typing, multilocus sequence typing, multilocus enzyme electrophoresis, and pulsed-field gel electrophoresis of enzyme-restricted DNA fragments can be useful epidemiologic tools during a suspected outbreak to detect concordance among invasive strains.
The incubation period is 1 to 10 days, usually less than 4 days.
Cultures of blood and cerebrospinal fluid (CSF) are indicated for patients with suspected invasive meningococcal disease. Cultures of a petechial or purpuric lesion scraping, synovial fluid, and other usually sterile body fluid specimens yield the organism in some patients. A Gram stain of a petechial or purpuric scraping, CSF, and buffy coat smear of blood can be helpful. Because N meningitidis can be a component of the nasopharyngeal flora, isolation of N meningitidis from this site is not helpful diagnostically. Bacterial antigen detection in CSF supports the diagnosis of a probable case if the clinical illness is consistent with meningococcal disease. A serogroup-specific polymerase chain reaction (PCR) test to detect N meningitidis from clinical specimens is used routinely in the United Kingdom, where up to 56% of cases are confirmed by PCR testing alone. This test particularly is useful in patients who receive antimicrobial therapy before cultures are obtained. In the United States, PCR-based assays are available in some research and public health laboratories.
Case definitions for invasive meningococcal disease are given in Table 3.36.
N meningitidis isolates with decreased susceptibility to penicillin have been identified sporadically from several regions of the United States and widely from Spain, Italy, and parts of Africa. Resistant meningococcal isolates for which the minimum inhibitory concentration to penicillin is more than 1 μg/mL are rare. Most reported isolates are moderately susceptible, with a minimum inhibitory concentration to penicillin of between 0.12 μg/mL and 1.0 μg/mL. Treatment with high-dose penicillin is effective against moderately susceptible strains. Cefotaxime and ceftriaxone show a high degree of in vitro activity against moderately penicillin-susceptible meningococci. In 2007 and 2008, the first ciprofloxacin-resistant strains of N meningitidis -causing disease were detected in certain areas of the United States. Laboratories are encouraged to conduct surveillance for antimicrobial-resistant isolates of meningococcal disease, especially serogroup B isolates. State and local health departments should notify the Centers for Disease Control and Prevention (CDC) if resistance to ciprofloxacin or other agents used for prophylaxis is detected.
The priority in management of meningococcal disease is the Treatment of shock in meningococcemia and of raised intracranial pressure in severe cases of meningitis. Empiric therapy with cefotaxime or ceftriaxone is recommended, because both meningococcemia and meningococcal meningitis are indistinguishable clinically from disease caused by other bacterial pathogens, including S pneumoniae . Once the microbiologic diagnosis is established, penicillin G is the drug of choice and should be administered intravenously (250 000-300 000 U/kg/day; maximum, 12 million U/day, divided every 4-6 hours) for patients with invasive meningococcal disease, including meningitis (see Chemoprophylaxis). Cefotaxime, ceftriaxone, and ampicillin are acceptable alternatives. Ceftriaxone is the most cost-effective agent (reduced nursing time and single daily dose), clears CSF rapidly, clears nasopharyngeal carriage effectively after 1 dose, and allows outpatient management for completion of therapy when appropriate. In a patient with a serious penicillin allergy characterized by anaphylaxis, chloramphenicol is recommended, if available. For travelers from areas such as Spain, where penicillin resistance has been reported, cefotaxime, ceftriaxone, or chloramphenicol is recommended. Five to 7 days of antimicrobial therapy is adequate. In meningococcemia presenting with shock, early and rapid fluid resuscitation and consideration of inotropic and ventilatory support may reduce mortality. In view of the lack of evidence in pediatric populations, adjuvant therapies are not recommended. The postinfectious inflammatory syndromes associated with meningococcal disease often respond to nonsteroidal anti-inflammatory drugs.
Isolation of the Hospitalized Patient
In addition to standard precautions, droplet precautions are recommended until 24 hours after initiation of effective antimicrobial therapy.
Care of Exposed People
Close contacts of all people with invasive meningococcal disease (see Table 3.37), whether endemic or in an outbreak situation, are at high risk and should receive chemoprophylaxis. The attack rate for household contacts is 500 to 800 times the rate for the general population. The decision to give chemoprophylaxis to contacts of people with meningococcal disease is based on risk of contracting invasive disease. Throat and nasopharyngeal cultures are of no value in deciding who should receive chemoprophylaxis and are not recommended.
Chemoprophylaxis is warranted for people who have been exposed directly to a patient's oral secretions through close social contact, such as kissing or sharing of toothbrushes or eating utensils as well as child care and preschool contacts during the 7 days before onset of disease in the index case. In addition, people who frequently slept in the same dwelling as the infected person within this period should receive chemoprophylaxis. For airline travel lasting more than 8 hours, passengers who are seated directly next to an infected person should receive prophylaxis. Routine prophylaxis is not recommended for health care professionals (Table 3.37) unless they have had intimate exposure to respiratory secretions, such as occurs with unprotected mouth-to-mouth resuscitation, intubation, or suctioning before or less than 24 hours after antimicrobial therapy was initiated. Chemoprophylaxis ideally should be initiated within 24 hours after the index patient is identified; prophylaxis given more than 2 weeks after exposure has little value.
Antimicrobial Regimens for Prophylaxis (see Table 3.38)
Rifampin, ceftriaxone, ciprofloxacin, and azithromycin are appropriate drugs for chemoprophylaxis in adults. The drug of choice for most children is rifampin (Table 3.38). If antimicrobial agents other than ceftriaxone or cefotaxime (both of which will eradicate nasopharyngeal carriage) are used for Treatment of invasive meningococcal disease, the child should receive chemoprophylaxis before hospital discharge to eradicate nasopharyngeal carriage of N meningitidis .
Ceftriaxone, given in a single intramuscular dose, has been demonstrated to be as effective as oral rifampin in eradicating pharyngeal carriage of group A meningococci. The efficacy of ceftriaxone has been confirmed only for serogroup A strains, but its effect likely is similar for other serogroups. Ceftriaxone has the advantage of ease of administration, which increases adherence, and is safe for use during pregnancy. Rifampin is not recommended for pregnant women.
Ciprofloxacin, administered to adults in a single oral dose, also is effective in eradicating meningococcal carriage (see Table 3.38). Ciprofloxacin is not routinely recommended for people younger than 18 years of age or for pregnant women; its use in infants and children may be justified after careful assessment of the risks and benefits for the individual patient (see Antimicrobial Agents and Related Therapy). In areas of the United States where ciprofloxacin-resistant strains of N meningitidis have been detected, ciprofloxacin should not be used for chemoprophylaxis. Ciprofloxacin resistance is being monitored, and updates for chemoprophylaxis will be made as needed. Use of azithromycin as a single oral dose has been shown to be effective for eradication of nasopharyngeal carriage and can be used on a limited basis where ciprofloxacin resistance has been detected.
Because secondary cases can occur several weeks or more after onset of disease in the index case, meningococcal vaccine is an adjunct to chemoprophylaxis when an outbreak is caused by a serogroup prevented by the vaccine. For control of meningococcal outbreaks caused by vaccine-preventable serogroups (A, C, Y, and W-135), the preferred vaccine in adults and children older than 2 years of age is tetravalent meningococcal (A, C, Y, and W-135) conjugate vaccine (MCV4), but the tetravalent meningococcal (A, C, Y, and W-135) polysaccharide vaccine (MPSV4) is acceptable. Meningococcal vaccines are being studied for use in children younger than age 2 years of age, and clinical trials of several serogroup B vaccines are underway.
There are 2 meningococcal vaccines licensed in the United States for use in children and adults against serotypes A, C, Y, and W-135, with a third being considered for licensure by the Food and Drug Administration. MPSV4 was licensed in 1981 for use in children 2 years of age and older. MPSV4 is administered subcutaneously as a single 0.5-mL dose and can be given concurrently with other vaccines but at different anatomic sites. The second vaccine, MCV4, was licensed in 2005 for use in people 11 through 55 years of age and in 2007 for children 2 through 10 years of age. MCV4 is administered intramuscularly as a single 0.5-mL dose and also can be given concurrently with other recommended vaccines. No vaccine is available in the United States for prevention of serogroup B meningococcal disease.
Serogroup A meningococcal polysaccharide vaccine, given as MPSV4, is immunogenic in children as young as 3 months of age, although the immune response in young children is not comparable to that seen in adults. For children younger than 18 months of age, 2 doses administered 3 months apart have been given for control of epidemics, although data regarding the efficacy of this schedule are not available. Serogroup A is a rare cause of invasive disease in the United States. Response to the other polysaccharides when MPSV4 is administered to infants younger than 24 months of age is poor.
In children 2 through 5 years of age, measurable concentrations of antibodies against group A and C polysaccharides decrease substantially during the first 3 years after a single dose of MPSV4. In school-aged children and adults, MPSV4-induced protection persists for at least 3 to 5 years.
Indications for Use of Meningococcal Vaccines (Table 3.39)
Routine childhood immunization with MCV4 is not recommended for children 2 through 10 years of age, because the infection rate is low in children in this age group, the immune response is poor in children 2 through 3 years of age, and the duration of immunity is not known. However, MCV4 is recommended for children 2 through 10 years of age who are in high-risk groups.
Recommendations for use of MCV4 are as follows:
- Adolescents 11 through 18 years of age should be immunized routinely with a single dose of MCV4.
- Adolescents should be immunized routinely at the 11- through 12-year health care visit, when immunization status (see Fig 1.2-27) and other preventive services can be addressed. Subsequent annual visits throughout adolescence also are recommended.
- People at increased risk of meningococcal disease should be immunized with MCV4 if they are at least 2 years of age. These people include:
- Children or adolescents who have terminal complement or properdin deficiencies or those who have anatomic or functional asplenia (see Children With Asplenia).
- Children or adolescents who travel to or reside in countries where N meningitidis is hyperendemic or epidemic (CDC Travelers' Health Hotline 877-FYI-TRIP or online at www.cdc.gov/travel).
- College freshmen living in dormitories.
- Military recruits.
- Because people with human immunodeficiency virus (HIV) infection are likely to be at higher risk of meningococcal disease, although not to the extent that they are at risk of invasive S pneumoniae infection, they may elect to be immunized with MCV4 if they are at least 2 years of age.
- People, including parents of children who wish to decrease their risk of meningococcal disease, may elect to receive MCV4 if they are 2 years of age or older.
- For control of meningococcal outbreaks caused by vaccine-preventable serogroups (A, C, Y, or W-135), MCV4 should be used for people 2 through 55 years of age, but MPSV4 is acceptable if MCV4 is not available.
- Immunization with MCV4 is preferred for children previously immunized with MPSV4 if at least 3 years have elapsed since receiving MPSV4.
- MCV4 is given to all military recruits in the United States.
Appropriate reimmunization intervals after MCV4 have yet to be determined. In children 2 years of age and older and adults, concentrations of bactericidal antibodies against serogroups A, C, Y, and W-135 3 years after a single dose of MCV4 are equal to or greater than bactericidal antibodies of people given MPSV4 6 months after immunization.Adverse Reactions and Precautions
Frequent adverse reactions after MPSV4 and MCV4 immunization include localized pain, irritability, headache, and fatigue. Most reactions are mild and resolve 3 days after immunization. Pain, induration, swelling, and redness at the injection site in 2- through 18-year-olds are slightly greater after administration of MCV4 compared with MPSV4. Fever is reported by 2% to 5% of adolescents who receive either MPSV4 or MCV4. Meningococcal immunization recommendations should not be altered because of pregnancy if a woman is at increased risk of meningococcal disease. Guillain-Barré syndrome (GBS) was reported in 22 adolescents aged 11 through 19 years who received MCV4 between June 2005 and October 2007.1
The temporal association provoked a recommendation that MCV4 should not be given to adolescents or adults with a history of GBS. The available data cannot determine with certainty whether MCV4 increases the risk for GBS and do not affect immunization recommendations. However, cases of GBS or other clinically significant adverse events after MCV4 should be reported to the Vaccine Adverse Event Reporting System (www.vaers.hhs.gov
). MPSV4 may be an acceptable alternative to MCV4 for people with a history of GBS.Reporting
All confirmed, presumptive, and probable cases of invasive meningococcal disease must be reported to the appropriate health department (see Table 3.36
). Timely reporting can facilitate early recognition of outbreaks and serogrouping of isolates so that appropriate prevention recommendations can be implemented rapidly.Counseling and Public Education
When a case of invasive meningococcal disease is detected, the physician should provide accurate and timely information about meningococcal disease and the risk of transmission to families and contacts of the infected person. Some experts recommend that patients with invasive meningococcal disease be evaluated for a terminal complement deficiency, and if a deficiency is detected, patients should receive MCV4 if 2 or more years of age, and patients and parents should be counseled about the risk of recurrent invasive meningococcal disease. Public health questions, such as whether a mass immunization program is needed, should be referred to the local health department. In appropriate situations, early provision of information in collaboration with the local health department to schools or other groups at increased risk and to the media may help minimize public anxiety and unrealistic or inappropriate demands for intervention.
a . see text.
b . People with anatomic or functional asplenia, terminal complement component (C5-C9) or properdin deficiencies, military recruits, and microbiologists routinely exposed to Neisseria meningitidis.
1 . Centers for Disease Control and Prevention. Update: Guillain-Barré syndrome among recipients of Menactra meningococcal conjugate vaccine-United States, June 2005-September 2006. MMWR Morb Mortal Wkly Rep . 2006;55(41):1120-1124 [PMID:17060898]
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